Recruitment and retention of patients in clinical trials are perennial challenges. By addressing the reasons as to why patients drop out of studies, attrition rates can be decreased.
In this post, we explore the most common reasons why patients tend to drop out of clinical trials and what sponsors and trial managers can do to keep patients enrolled for the duration of the study.
Trials that require patients to pay money can deter many from participating. Research suggests cost can be a major cause of attrition, writes healthcare reporter Sarah Gantz. According to research from Fox Chase Cancer Center, 1,200 surveyed cancer clinical trial patients regard money spent to participate as a big issue. This is even more so for critically ill patients who expect treatments to be expensive.
Part of the problem is patients’ fear over what their insurance will cover. However, Pat Jolley, director of clinical initiatives at the Patient Advocate Foundation, tells Gantz that private insurers typically cover any treatment patients receive as standard of care for their condition and sponsors pay for the new therapy. “Clinical investigators typically check that participants are covered by in-network health plans, but if you’re considering enrolling in a trial, it is worth calling your insurance company to ask.”
Out-of-pocket costs, including money spent on travel and accommodation, time away from work, and the need to secure child care, are other potential barriers to patients’ participation.
Part of the problem is that patients aren’t always aware of the costs involved until they’re already enrolled. When they see the rising costs, they abandon the study, explains Kyle Cunningham, chief product officer at clinical trial payment software company Greenphire.
He concedes that many sponsors do reimburse patients, but not all do so in timely or convenient ways. For example, patients have said they’d favor reloadable debit cards for immediate reimbursement. Timely payments — instead of waiting weeks or even months — could help to ensure more patients remain enrolled in the study.
Noelle B. Smith, Ph.D., headed a study published in Frontier in Psychology called “Predictors of Dropout From Residential Treatment for Posttraumatic Stress Disorder Among Military Veterans.” She notes that psychotherapy treatment has a dropout rate of 50-70 percent.
Some of the factors involved in patient dropout include the therapy setting and type of treatment. The research also indicates that the severity of a patient’s symptoms affects their participation. The more severe the symptoms the less likely patients will remain in therapy.
While this study focuses on a specific patient population, there is potentially a transferrable lesson: Those most in need might see their condition as a hindrance to receiving treatment for their condition.
The Medical Device Innovation Consortium (MDIC) wanted to formulate guidelines to include patients in the design phases of clinical trials. When asking patients and medical device manufacturers about patient engagement for trial design, results were disappointing.
For example, more than half of the industry stakeholder respondents had never consulted patients before designing the trial protocol, ICON’s Matthew McCarty and Michael Otlewski of the MED Institute, explain. Further results showed 28 percent obtained patient input 25 percent of the time. As many as 80 percent had never or less than 25 percent of the time sought patient input for operational study design.
It’s clear that trials suffer greater risk of patient attrition when patients’ needs have not been considered when designing the trial.
It’s hard enough for patients to try to manage their medical conditions without the additional responsibilities of participating in research. The result is that some patients don’t adhere to the treatment and soon drop out of the study. Jessica Kent, at Health IT Analytics, says improving adherence will also improve retention.
She refers to a study published in Trends in Pharmacological Science that lists the struggles of maintaining adherence records and other data capture during a study. So it makes sense to simplify adherence — and this is something technology can help with. Wearable devices and video monitoring, for instance, automates data collection and removes the responsibility of tracking and reporting from patients.
“Machine learning and deep learning models can then analyze this data in real time, logging any relevant events for clinical trial investigators. What’s more, clinical trial administrators could even use AI techniques to predict the dropout risk for some patients,” Kent writes.
Retention can be improved by simplifying patient consent. The clearer the consent form, the easier patients understand what they’re agreeing to and the more likely they will remain enrolled in the study, Anne White, president of Lilly Oncology, tells Clinical Leader’s Ed Miseta.
“Simplified consent forms don’t just demystify the trial. They actually have a profound impact on retention. If patients do not understand what they are consenting to, it is easy for them to later say the trial is not what they signed up for. If that situation arises, you lose the patient. A simplified consent form can prevent that situation. If patients understand what they are consenting to, they will be more willing to stick with it,” White explains.
Consent forms written in plain language is a step in the right direction, Miseta says, pointing out that Eli Lilly is trialling this approach together with videos to explain protocols and procedures. Another is having those consent forms available to submit online.
Sponsors can improve accessibility to clinical trials by simplifying protocols and including only those procedures and tests that support primary endpoints and patient safety. The result will be fewer site visits and intrusions into patients' lives, writes Jeffrey S. Kasher, Ph.D., president of Patients Can’t Wait.
Accessibility can also be improved by locating trial sites in socioeconomically and geographically diverse communities or removing physical sites altogether by replacing them with virtual trials.
The main focus for sponsors should be how to make trial designs more flexible so a greater number of patients can enroll and commit to a study until its completion. That might require a hybrid trial of sites and virtual offerings. Another option, Kasher explains, is clinical research as a care option.
Clinical research as a care option essentially keeps patients in their routine care setting so they feel more familiar and in control of their treatment. It’s a great example of patient-centricity with patients’ convenience at the heart of the design.
Improving accessibility also means making trials more demographically diverse. Yet elderly patients, those with limited mobility and patients from ethic and racial minorities are often excluded from research, explain Beatrice Huang et al in an article published in BMC Medical Research Methodology. “Three key strategies to maximize recruitment and retention were identified during the study: incorporating the patient perspective, partnering with the community clinics, and building patient rapport.”
Patients face many burdens when participating in a clinical trial and appreciate any actions taken to ease their stress and inconvenience. Not only will removing burdens make it easier for patients to manage their participation, it will show them that they are valued, Jim Murphy, CEO at Greenphire, explains.
So whether sponsors quickly reimburse patients for costs expended or engage them throughout the trial’s various stages, they will see that trial staff care. Removing burdens won’t guarantee an end to attrition but it will certainly help.
Patients can offer researchers personal advice on what it means to live with a particular condition. They may not understand the finer medical details but their insight will help researchers provide better treatment plans and design more manageable clinical trials.
For instance, researchers understand that gout is a chronic disease that requires long-term management. Patients, on the other hand, may regard it as an episodic disease, which needs treatment only during flare ups, says pharmaceutical marketing and strategic communications professional Sandy Chase. Knowing the discrepancy between these two perspectives is key to providing patients with the knowledge necessary to improve how they manage their conditions.
Researchers could show patients that they need treatment throughout their lives not just at the worst moments of the disease. Patients may then be more inclined to remain enrolled in a treatment plan until the study has been completed.
Patient attrition remains a costly and time-consuming issue facing clinical trial sponsors and research teams. Much can be learned from patients who drop out of studies. Interviewing those patients who leave can yield insight as to their reasons for doing so.
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